Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Metastatic breast cancer (MBC) remains a terminal illness for which major treatment advances are slow to appear, and hence it is crucial that effective palliative interventions be developed to reduce the cancer-related symptoms of women with this condition during the remaining years of their lives. This pilot/feasibility study examined a novel, yoga-based palliative intervention, the Yoga of Awareness Program, in a sample of women with MBC. The eight-week protocol included gentle yoga postures, breathing exercises, meditation, didactic presentations, and group interchange. Outcome was assessed using daily measures of pain, fatigue, distress, invigoration, acceptance, and relaxation during two preintervention weeks and the final two weeks of the intervention. Thirteen women completed the intervention (mean age=59; mean time since diagnosis=7 years; two African American, 11 Caucasian). During the study, four participants had cancer recurrences, and the physical condition of several others deteriorated noticeably. Despite low statistical power, pre-to-post multilevel outcomes analyses showed significant increases in invigoration and acceptance. Lagged analyses of length of home yoga practice (controlling for individual mean practice time and outcome levels on the lagged days) showed that on the day after a day during which women practiced more, they experienced significantly lower levels of pain and fatigue, and higher levels of invigoration, acceptance, and relaxation. These findings support the need for further investigation of the effects of the Yoga of Awareness Program in women with MBC.
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PMID:Yoga for women with metastatic breast cancer: results from a pilot study. 1734 3

The combination of docetaxel and cisplatin has shown promising results in anthracycline-pretreated patients with advanced breast cancer, but with substantial toxicity. The efficacy and safety in anthracycline-naive patients has not been evaluated. Between October 2003 and January 2006, we enrolled 39 patients. None had undergone chemotherapy for metastatic disease or been exposure to adjuvant anthracycline-based regimens earlier. Eligibility criteria included: histologically proven metastatic cancer; WHO performance status (PS) 0-2; and adequate hematological, hepatic and renal function. Docetaxel (70 mg/m) and cisplatin (50 mg/m) were administered every 3 weeks until the patient either refused to continue, or progression, or even unacceptable toxicity occurred. Tumor response was assessed every three cycles. One patient was withdrawn from response analysis because of toxicity. Thirty-eight patients had a complete tumor assessment. Median age was 50 years (range, 28-63); 5.1% had a WHO of PS of 0; 87% a PS of 1; 7.7% a PS of 2; in 69%, two or more organs were involved. A total of 291 cycles (range, 1-9) were administered. Three complete responses and 27 partial responses (intent-to-treat response rate 30/39=76.9%) resulted; disease remained stable in six patients and two had disease progression. Grade III/IV toxicities included diarrhea in 10.2%, asthenia/fatigue in 2.5%, mucositis in 5.1% and neutropenia in 87.3% of patients. Seven patients developed febrile neutropenia (17.9%). The median time to progression was 11.2 months; the timespan was not sufficient to track the median survival. Docetaxel/cisplatin is an active regimen with acceptable toxicity in the first-line treatment of metastatic breast cancer, but it is not sufficiently promising as a standard. Further randomized study is warranted.
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PMID:An open-labeled phase II trial of docetaxel in combination with cisplatin as first-line cytotoxic therapy for anthracycline-naive patients with metastatic breast cancer. 1789 23

Gemcitabine and cisplatin are the active agents in metastatic breast cancer pretreated with anthracycline and/or taxane as a second line treatment. The present study was designed to assess the efficacy and safety of this regimen given biweekly schedule in these patients. Twenty-seven women, median age 57, with metastatic breast cancer previously treated with anthracycline and taxane were eligible for enrollment. Gemcitabine was administered intravenously on days 1 and 15 at a dose of 2,000 mg/m(2) and Cisplatin was given intravenously on day 1 and 15 at a dose of 50 mg/m(2). Treatment cycles were repeated on an outpatient basis every 28 days. Of all 27 evaluable patients, the overall response rate was 26% (7 of 27; 95% CI: 11-46%) with seven all partial responses. The stable diseases were found in 9 (33%) patients. At the time of last follow-up, 11 (41%) of the patients died of their disease progression. The median overall survival duration was 7.4 +/- 2.8 months. The 1-year overall survival rate was 46.9% +/- 12.3. Hematological toxicity was not found as the principal dose-limiting toxicity. Severe (grade III/IV) neutropenia was observed only one (4%) patients. No patient was complicated by febrile neutropenia and G-CSF usage was not performed. Grade III and IV anemia were seen in only 4 (15%) and thrombocytopenia was noted only one (4%) patients. Severe hepatic (n = 2) and renal toxicity (n = 1) were observed and these all recovered completely without complication. Several other severe non-hematological side effects were managed easily. Permanent dose reductions were necessary in 9 (33%) patients and chemotherapy administration was also delayed in 7 (26%) patients because of delayed both hematological and non-hematological toxicity recovery. Treatment was discontinued in one (4%) patient due to severe fatigue and deteriorating performance status. In conclusion, gemcitabine and cisplatin combination therapy with this biweekly schedule and dosage is moderately active and extremely safe in patients with metastatic breast cancer previously treated with anthracycline and taxanes.
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PMID:Biweekly administration of gemcitabine and cisplatin chemotherapy in patients with anthracycline and taxane-pretreated metastatic breast cancer. 1816 64

Breast cancer is the second leading cause of cancer death in women. Treatment options for advanced-stage disease, although numerous, remain suboptimal. Lapatinib and ixabepilone are two new agents approved by the United States Food and Drug Administration (FDA) in 2007 for the treatment of locally advanced breast cancer (LABC) or metastatic breast cancer (MBC). When added to the existing endocrine therapies-single--agent cytotoxic therapies and combination chemotherapy regimens--lapatinib and ixabepilone offer potential treatment strategies for disease that has become resistant to trastuzumab and the taxanes, respectively. Lapatinib is an oral dual tyrosine kinase inhibitor against members of the human epidermal growth factor receptor (HER) family (HER1 or epidermal growth factor receptor [EGFR], and HER2). It is indicated for combination therapy with capecitabine for the treatment of patients with HER2-overexpressing LABC or MBC whose disease has progressed after receiving previous treatment with an anthracycline, a taxane, and trastuzumab. Of note, lapatinib is the first FDA-approved tyrosine kinase inhibitor indicated for use in MBC. Ixabepilone, the first FDA-approved analog of the antimicrotubule agent epothilone B, is indicated as monotherapy for the treatment of LABC or MBC in patients whose tumors are refractory or resistant to anthracyclines, taxanes, and capecitabine. It is also indicated in combination with capecitabine for treatment of LABC or MBC that is resistant to anthracycline and taxane. Both lapatinib and ixabepilone are fairly well tolerated. The most common toxicities with lapatinib are diarrhea (65%) and hand-and-foot syndrome (53%), whereas peripheral neuropathy (62%), fatigue (56%), and neutropenia (54%) are most common with ixabepilone. Though the conventional standard end point of overall survival has not yet been assessed in clinical trials, these agents have been shown to improve surrogate markers of clinical benefit: progression-free survival and the related time to progression. Future clinical trials should focus on elucidation of optimal combination or sequential therapies, as well as patient-specific therapies based on tumor characteristics, such as biomarkers and tumor subtypes.
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PMID:Lapatinib and ixabepilone for the treatment of metastatic breast cancer. 1882 21

Vandetanib is a novel, orally available inhibitor of different intracellular signaling pathways involved in tumor growth, progression, and angiogenesis: vascular endothelial growth factor receptor-2, epidermal growth factor receptor, and REarranged during Transfection tyrosine kinase activity. Phase I clinical trials have shown that vandetanib is well tolerated as a single agent at daily doses < or =300 mg. In the phase II setting, negative results were observed with vandetanib in small cell lung cancer, metastatic breast cancer, and multiple myeloma. In contrast, three randomized phase II studies showed that vandetanib prolonged the progression-free survival (PFS) time of patients with non-small cell lung cancer (NSCLC) as a single agent when compared with gefitinib or when added to chemotherapy. Rash, diarrhea, hypertension, fatigue, and asymptomatic QTc prolongation were the most common adverse events. Antitumor activity was also observed in medullary thyroid cancer. Four randomized phase III clinical trials in NSCLC are exploring the efficacy of vandetanib in combination with docetaxel, the Zactima in cOmbination with Docetaxel In non-small cell lung Cancer (ZODIAC) trial, or with pemetrexed, the Zactima Efficacy with Alimta in Lung cancer (ZEAL) trial, or as a single agent, the Zactima Efficacy when Studied versus Tarceva (ZEST) and the Zactima Efficacy trial for NSCLC Patients with History of EGFR-TKI chemo-Resistance (ZEPHYR) trials. Based on a press release by the sponsor of these trials, the PFS time was longer with vandetanib in the ZODIAC and ZEAL trials; the ZEST trial was negative for its primary superiority analysis, but was successful according to a preplanned noninferiority analysis of PFS. Ongoing phase II and III clinical trials will better define the appropriate schedule, the optimal setting of evaluation, and the safety of long-term use of vandetanib.
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PMID:Vandetanib (ZD6474), a dual inhibitor of vascular endothelial growth factor receptor (VEGFR) and epidermal growth factor receptor (EGFR) tyrosine kinases: current status and future directions. 1934 11

This randomized phase-II trial investigated the efficacy and tolerability of weekly docetaxel or paclitaxel in metastatic breast cancer (MBC) patients considered unfit for a 3-weekly therapy. The primary study endpoint was antitumor activity, the second endpoint was tolerability, time to progression (TTP) and overall survival (OS). In intent-to-treat analysis, we observed for paclitaxel and docetaxel respectively partial response (PR) in 48% versus 38%, stable disease (SD) in 24% versus 16%, PD in 15% versus 30%. Median TTP was 21.1 weeks versus 12.7 weeks and median OS 55.7 weeks versus 32 weeks. Toxicity profiles were acceptable with more anemia and neurotoxicity for paclitaxel and more edema and fatigue for docetaxel. In patients with MBC unfit for 3-weekly docetaxel or paclitaxel, weekly administration of either compound may certainly be considered. They display different, but acceptable toxicity profiles, with levels of antitumoral efficacy comparable to those previously reported for 3-weekly regimens.
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PMID:Weekly paclitaxel versus weekly docetaxel in elderly or frail patients with metastatic breast carcinoma: a randomized phase-II study of the Belgian Society of Medical Oncology. 1965 23

This trial was conducted to assess the efficacy and safety of sorafenib in patients with metastatic breast cancer. In this multinational, open-label phase II study, patients with metastatic breast cancer that had progressed after at least one prior chemotherapy regimen were continuously treated with oral sorafenib, 400 mg twice daily. The primary endpoint was overall best response; a secondary endpoint was percentage of patients with stable disease for greater than or equal to 16 weeks. Biomarker analysis were also performed. Of the 56 patients enrolled into the study, 54 were treated with at least one dose of sorafenib. Partial response was observed in one patient (2%) and stable disease in 20 patients (37%); no complete responses were observed. Disease stabilization for greater than or equal to 16 weeks was seen in 12 patients (22%); stabilization for greater than or equal to 6 months in seven patients (13%). The most common drug-related grade 3 adverse events were rash/desquamation (6%), hand-foot skin reaction (4%), and fatigue (4%). Baseline vascular endothelial growth factor levels, levels of soluble epidermal growth factor receptor during treatment and both baseline and changes in soluble human epidermal growth factor receptor 2 levels correlated significantly with clinical outcomes. Although the primary endpoint of overall response rate showed minimal improvement on sorafenib 400 mg twice-daily treatment, the rate of disease stabilization was encouraging in patients treated with one or more lines of chemotherapy. The treatment had a clinically manageable toxicity profile. Further investigation of single-agent sorafenib in this patient population is not recommended; however, studies investigating combinations of sorafenib with chemotherapeutic agents are warranted and ongoing.
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PMID:Phase II multicenter, uncontrolled trial of sorafenib in patients with metastatic breast cancer. 1973 18

PURPOSE Ixabepilone (BMS-247550) is a microtubule-stabilizing epothilone B analog with activity in taxane-resistant metastatic breast cancer. The Gynecologic Oncology Group conducted a phase II evaluation of the efficacy and safety of ixabepilone in patients with recurrent or persistent platinum- and taxane-resistant primary ovarian or peritoneal carcinoma. PATIENTS AND METHODS Patients with measurable platinum- and taxane-resistant ovarian or peritoneal carcinoma, defined as progression during or within 6 months of one prior course of treatment with each agent, received intravenous ixabepilone 20 mg/m(2) administered over 1 hour on days 1, 8, and 15 of a 28-day cycle. Results Of 51 patients entered, 49 were eligible. The objective response rate was 14.3% (95% CI, 5.9% to 27.2%), with three complete and four partial responses. Twenty patients (40.8%) had stable disease, whereas sixteen (32.7%) had increasing disease. The median time to progression was 4.4 months (95% CI, 0.8 to 32.6+ months); median survival was 14.8 months (95% CI, 0.8 to 50.0) months. Patients received a median of two treatment cycles (range, 1 to 29 cycles), and 18.4% of patients received > or = six cycles. Adverse effects included peripheral grade 2 (28.5%) and grade 3 (6.1%) neuropathy, grades 3 to 4 neutropenia (20.4%), grade 3 fatigue (14.3%), grade 3 nausea/emesis (22%), grade 3 diarrhea (10%), and grade 3 mucositis (4%). CONCLUSION Ixabepilone 20 mg/m(2) over 1 hour on days 1, 8, and 15 of a 28-day cycle demonstrates antitumor activity and acceptable safety in patients with platinum- and taxane-resistant recurrent or persistent ovarian or primary peritoneal carcinoma.
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PMID:Phase II clinical trial of ixabepilone in patients with recurrent or persistent platinum- and taxane-resistant ovarian or primary peritoneal cancer: a gynecologic oncology group study. 1991 61

Immunomodulation with cytokines was used to improve the result of high-dose chemotherapy (HDC)/autologous hematopoietic stem cell transplantation (AHST). We examined the use of IL-2 and growth factors for mobilization, ex vivo activation of peripheral blood stem cell (PBSC) and maintenance therapy after HDC/AHST in metastatic breast cancer. Eligible patients with metastatic breast cancer for HDC/AHST were assigned to 1 of 3 protocols for PBSC mobilization: G-CSF (group 1); IL-2 + G-CSF (group 2); or IL-2 + G-CSF + GM-CSF (group 3). HDC with cyclophosphamide, carmustine and thiotepa was given from day -7 to -5. PBSCs were treated ex vivo with IL-2 for 24 h and reinfused on day 0. Maintenance therapy included low-dose IL-2, followed by 2 courses of intermediate-dose IL-2. GM-CSF was given from day 1 until neutrophil recovery. Thirty-four patients (10 in group 1, 14 in group 2, and 10 in group 3) were included. Comparable numbers of CD34(+) cells were collected from all 3 groups; incremental increases of CD3(+) cells were collected from groups 1 to 2 and to 3 (p = 0.03). Major adverse effects from IL-2 were fever, hypotension and fatigue; no treatment-related mortality was seen. At a median follow-up of 790.5 days (range 150-2,722 days), median progression-free survival was 434 days and median overall survival was 1,432 days. Estimated 3-year progression-free and overall survival rates were 31 and 57%. Our study suggested that the use of IL-2 and growth factors immunomodulation with HDC/AHST was feasible with comparable survival rates.
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PMID:Interleukin-2 and granulocyte-macrophage-colony-stimulating factor immunomodulation with high-dose chemotherapy and autologous hematopoietic stem cell transplantation for patients with metastatic breast cancer. 1999 65

The epothilone B analogue, ixabepilone, binds to b-tubulin, is effective for taxane-refractory metastatic breast cancer (MBC), and may be given every 3 weeks or weekly. We evaluated the efficacy of weekly ixabepilone (I) plus trastuzumab (T) and carboplatin (C) as first line therapy in HER2 + MBC. Patients with HER2+ (3+ by IHC or FISH amplified) MBC received I (15 mg/m2 IV) and C (area under the curve, AUC = 2 IV) on days 1, 8, and 15 of a 28-day cycle for a maximum of 6 cycles, plus weekly T (4 mg/kg loading dose then 2 mg/kg IV) during chemotherapy then every 3 weeks (6 mg/kg IV) until disease progression. The primary objective was to determine whether the combination was associated with a response rate (RR) of at least 75%. Fifty-nine patients were treated, and 39 had HER2 overexpression confirmed in a central lab (cHER2+). For all treated patients, objective response occurred in 26 patients (44%; 95% CI 31-58%), median time to progression was 8.2 months (95% CI 6.3-9.9), and median overall survival was 34.7 months (95% CI 25.7 to [not reached]). Results were comparable for cHer2? cancers. Grade 3-4 adverse events included neutropenia (49%), thrombocytopenia (14%), fatigue (12%), nausea (7%), diarrhea (7%), and neuropathy (7%). One patient died from treatment complications during cycle 1. Weekly ixabepilone and carboplatin plus trastuzumab have an acceptable toxicity profile, but are not likely to be associated with an RR of 75% in HER2+ MBC. Efficacy appears comparable to paclitaxel, carboplatin, and trastuzumab.
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PMID:A phase II trial of trastuzumab plus weekly ixabepilone and carboplatin in patients with HER2-positive metastatic breast cancer: an Eastern Cooperative Oncology Group Trial. 2001 54


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